The technology to simultaneously genotype hundreds of thousands of single nucleotide polymorphisms (SNPs) in a single assay has only recently been developed and has the potential to revolutionize our ability to identify disease-associated genes in complex diseases. Specifically, high density SNP genotyping opens the possibility for case-control genome-wide association studies whereby SNPs that are evolutionary associated with a complex multigenic disease, and also in close physical proximity to a functional mutation, can be discovered. The major drawback of genome-wide association studies is that they require hundreds to thousands of cases and well matched controls for sufficient powering. This type of study is expected to cost millions of dollars using individual genotyping. The overall goal of this proposal is to develop cost effective design strategies and accompanying analysis tools for genome-wide case-control SNP association studies using pooled genomic DNA. [unreadable] [unreadable] We will develop new analysis tools and design strategies for genome-wide association studies using our unparalleled access to high-density genome-wide SNP genotyping data. Within the past six months, we have conducted genome-wide microarray SNP scans on over 5,000 samples. We are currently an early access site for the Affymetrix 500K Mapping array and have already completed two genome-wide scans on pooled DNA using this platform, verifying a previously known disease locus for Progressive Supranuclear Palsy (PSP) and identifying several new loci. We will have access to datasets from multiple genome-wide association studies on pooled genomic DNA including hypertension, Alzheimer's Disease (AD), autism, bipolar disorder, melanoma, PSP, memory, and diabetes. For AD, we will have access to both pooled and individual genotypes for 500K+ SNPs in 1,000 cases and 1,000 controls. Additionally, we have included funding within this proposal for genome-wide association studies on pooled genomic DNA for samples and diseases as decided by the steering community. In the course of this study, we will deliver web-based content and software tools that: (1) aid in the overall design of genome-wide association studies whereby using pooled genomic DNA is one approach; (2) provide quality control metrics for genotyped samples; and (3) automate analysis of a genome-wide association study data from pooled genomic samples. [unreadable] [unreadable] [unreadable]